The present invention relates to a crosslinked gelatin gel preparation containing a basic fibroblast growth factor (to be abbreviated as xe2x80x9cbFGFxe2x80x9d hereinafter).
In 1976, bFGF was found in bovine pituitary gland by Gospodarowicz as a protein which highly stimulates the proliferation of fibroblast (Nature, Vol. 24, page 124, 1974). Then, bFGF-coding genes have been cloned so that bFGF can be produced in large quantities by genetic recombination technologies, and bFGF has been therefore energetically studied. As a result, it has been revealed that bFGF simulates the proliferation of a variety of cells such as capillary endotherial cells, blood vessel smooth muscle cells, cornea endothelial cells, osteoblast and chondrocyte as well as the proliferation of fibroblast.
Like other polypeptides and proteins, however, bFGF has a short in vivo half-life, and fails to provide an effect as expected when administered as an aqueous solution. It is therefore desirable to formulate bFGF as a sustained release preparation which can stabilize bFGF and can gradually release bFGF for a definite period of time. The present inventors have been therefore engaged in the development of sustained release carriers for formulating bFGF as a sustained release preparation.
In recent years, sustained release preparations of physiologically active peptides and proteins have been extensively studied, and as sustained release carriers therefor, there are synthetic polymers that can undergo degradation by a living body, such as polyglycolic acid.lactic acid and polyanhydride, and natural polymers that can undergo in vivo degradation and absorption, such as polysaccharides and proteins.
The natural polymers that can undergo in vivo degradation and absorption have excellent suitability to a living body and cause almost no stimulation to a living body so that they are preferred as sustained release carriers. Since, however, most of these natural polymers are water-soluble, they are not suitable as a sustained release insolubilizing carrier for bFGF which is a water-soluble physiologically active peptide.
The present inventors have therefore made studies for water-insolubilizing natural polymers that can undergo in vivo degradation and absorption, by some method in order to obtain some which can be used as a sustained release insoluble carrier for bFGF.
As a result, it has been found that a crosslinked gelatin gel insolubilized in water by crosslinking a gelatin which is a natural polymer that can undergo in vivo degradation and absorption, is suitable as a sustained release carrier for bFGF, and the present invention has been accordingly completed.
That is, the gist of the present invention consists in a crosslinked gelatin gel preparation containing a basic fibroblast growth factor.
The present invention characteristically provides a sustained release preparation of bFGF, which can achieve a desired sustained release rate as required, on the basis of a crosslinked gelatin gel which has excellent suitability to a living body, causes almost no stimulation on a living body and has excellent properties as a sustained release carrier. The sustained release rate can be varied depending upon the crosslinking degree of a gelatin, the water content of the crosslinked gelatin and the properties of a used gelatin (isoelectric point, etc.).